Obesity is a major health problem in the United States and results in increased incidence of various diseases including cardiovascular and gallbladder disease, diabetes mellitus, and of premature death. The underlying cause of obesity is a consistent excess in caloric intake relative to energy expenditure leading to accumulation of fat. A possible satiety agent, cholecystokinin (CCK), which is released from the duodenum upon consumption of food, has been shown to decrease food intake in rats, monkeys and man. In these experiments it is proposed to measure the effect on feeding behavior of obese Zucker rats of CCK administered as a single intraperitoneal injection or as a continuous intravenous injection. Body weight of obese and lean rats will be decreased by food intake restriction and increased by ventromedial hypothalamic lesions to measure these effects on the response to CCK. Hormonal and metabolic responses following intraperitoneal injection of obese and lean rats will be compared. Since various parameters of the obese change at the early ages, their responses to CCK will be measured with age starting form the third week. The response of obese animals to CCK will be compared to their response to 2 other anorectic agents, fenfluramine and amphetamine, on feeding behavior. Since antianxiety drugs are often combined with anorectic agents, the effects of combinations of diazepam, also a food intake stimulant, with CCK on feeding behavior will be measured. The obese Zucker rat has been shown to be less sensitive to the food intake depressing effect of CCK; these experiments should help confirm this response and more specifically how it occurs, e.g. decreased meal size. The results will show in what ways the obese rat responds differently from the normal to CCK, a natural satiety agent, and may lead to a better understanding of the underlying causes of obesity and consequently perhaps better control of this health problem.